Genomewide analysis of copy number variants in alopecia areata in a Central European cohort reveals association with MCHR2
Genomewide analysis of copy number variants in alopecia areata in a Central European cohort reveals association with MCHR2
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DOI：
10.1111/exd.13123
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发表时间：
2017-06-01
影响因子：
3.6
通讯作者：
Betz, Regina C.
中科院分区：
文献类型：
--
作者：
Fischer, Johannes;Degenhardt, Franziska;Betz, Regina C.
斑秃（AA）是一种常见的自身免疫性脱发疾病，常导致明显的心理困扰。对AA病理生理学的了解正在增加，部分原因是最近的遗传学发现涉及几个遗传基因座的常见变异。到目前为止，还没有研究调查拷贝数变异（CNVs）的AA，一个突出的类别的基因组变异参与其他自身免疫性疾病的贡献。在这里，我们报告了一个全基因组和一个候选基因为重点的CNV分析进行了队列的585例AA患者和1340控制中欧血统。在以下五个染色体区域发现CNVs与AA名义上显著相关：4q35.2，6q16.3，9 p23，16p12.1和20p12.1。最有希望的发现是6q16.3中的342.5-kb相关区域（在4/585例患者中重复; 0/1340对照）。重复跨越基因MCHR 2和MCHR 2-AS 1，涉及黑色素浓缩激素（MCH）信号传导。这些基因在以前的AA发病机制研究中没有涉及。然而，先前的研究表明，MCHR 2通过诱导黑色素聚集来影响barfin flounder鱼的鳞片颜色。AA优先影响有色头发，AA患者的头发在AA急性发作后再生时经常显示颜色变化。这可能表明AA，色素沉着和MCH信号之间的关系。总之，本研究结果提供了提示性证据，参与MCHR 2在AA发病机制的重复。
Alopecia areata (AA) is a common hair loss disorder of autoimmune aetiology, which often results in pronounced psychological distress. Understanding of the pathophysiology of AA is increasing, due in part to recent genetic findings implicating common variants at several genetic loci. To date, no study has investigated the contribution of copy number variants (CNVs) to AA, a prominent class of genomic variants involved in other autoimmune disorders. Here, we report a genomewide- and a candidate gene-focused CNV analysis performed in a cohort of 585 patients with AA and 1340 controls of Central European origin. A nominally significant association with AA was found for CNVs in the following five chromosomal regions: 4q35.2, 6q16.3, 9p23, 16p12.1 and 20p12.1. The most promising finding was a 342.5-kb associated region in 6q16.3 (duplications in 4/585 patients; 0/1340 controls). The duplications spanned the genes MCHR2 and MCHR2-AS1, implicated in melanin-concentrating hormone (MCH) signalling. These genes have not been implicated in previous studies of AA pathogenesis. However, previous research has shown that MCHR2 affects the scale colour of barfin flounder fish via the induction of melanin aggregation. AA preferentially affects pigmented hairs, and the hair of patients with AA frequently shows a change in colour when it regrows following an acute episode of AA. This might indicate a relationship between AA, pigmentation and MCH signalling. In conclusion, the present results provide suggestive evidence for the involvement of duplications in MCHR2 in AA pathogenesis.